1. Field of the Invention
This invention generally relates to a noninvasive method of quantitatively determining the concentration of components in a light- or other radiation-scattering environment. A novel means of varying temperature or other parameters to assist in determinations is presented.
More particularly, the invention relates to spectrophotometry systems and measurements of behavior, action or function of substances which are affected by temperature or other variables.
A method and device for the continuous monitoring of blood parameters is especially disclosed. This technology makes use of measurement of temperature-induced changes in the respiratory molecule hemoglobin to determine acid-base balance and other parameters.
2. Description of the Related Art
There is no device currently known which can noninvasively measure pH and/or blood gases.
In a broad context, differential thermal analysis is a technique used in analytical chemistry for identifying and quantitatively analyzing the chemical composition of substances by observing the thermal behavior of a sample as it is heated. This methodology is widely used for identifying minerals and mineral structures, but is not performed noninvasively and is in fact usually destructive to the sample being tested. It is not useful in biologic applications. Similarly, related thermometric methods such as thermogravimetry, calorimetry, and cryoscopy are not related to the present invention.
Induction of temperature changes has been used in the experimental study of chemical kinetics to facilitate measurement of reaction rates. The technique described herein does not depend upon any chemical reaction taking place.
Temperature is a very important factor in the chemistry of both biologic and non-biologic systems. It reckons in the speed of reactions; indeed, if a reaction will occur at all. Temperature can be relatively easy to both measure and regulate. Furthermore, changing the temperature of a substance or system does not normally damage the substance in any way (within a certain range; clearly temperature extremes will harm almost any system). Temperature by itself can affect acid-base balance and pH because of a direct affect on the hydrogen ion.
Spectrophotometry is a commonly used technique for the identification and quantification of substances. It is used in medicine in the form of pulse oximetry, to determine the ratio of oxyhemoglobin to deoxyhemoglobin and thus measure the oxygenation status of a patient. Spectrophotometry deals with measurement of the radiant energy transmitted or reflected by a body as a function of the wavelength. Infrared (IR) spectroscopy passes infrared light through an organic molecule and produces a spectrum that can be plotted as the amount of light transmitted versus the wavelength of infrared radiation. Since all bonds in an organic molecule interact with infrared radiation, IR spectra provide a great deal of structural data, allowing identification to be made. There is a large area of prior art relating to spectrophotometry and, more specifically, to oximetry. The most relevant prior art known by the inventor is reviewed below, but none relate to the unique determinations made possible by the method and device disclosed in this application.
U.S. Pat. No. 5,431,159, issued Jul. 11, 1995 to Baker et al, describes methods of improving measurements made by standard pulse oximetry. While these devices may improve the signal quality and signal-to-noise ratio for oximeter calculations, they do not allow for any new determinations, as outlined in the present application.
U.S. Pat. No. 5,101,825, issued Apr. 7, 1982 to Gravenstein et al, purports to measure hemoglobin noninvasively by means of simultaneous measurement of volume changes and changes in the mass of hemoglobin species measured by oximetry. It is unclear how blood volume changes could be determined to the desired accuracy.
U.S. Pat. No. 5,499,627, issued Mar. 19, 1996 to Steuer et al, claims a system for noninvasive hematocrit monitoring. The patent describes techniques of measuring the infrared absorption of hemoglobin at isobestic points of the oxy and deoxy species. However, there is no discussion relating to the use of temperature changes and, therefore, Steuer et al. is not particularly relavent to the present invention.
U.S. Pat. No. 5,427,093, issued Jun. 27, 1995 to Ogawa et al, describes a device to disperse heat generated by the LED in an oximeter probe by means of a heat-dissipating plate. This is a potential benefit for standard pulse oximeters, but in no way improves their measurements or allow for new determinations, as in the device and method described herein.
U.S. Pat. No. 4,167,331, issued Sep. 11, 1979 to Nielsen, teaches the use of multiple wavelength techniques for identification of multiple absorbing substances.
Several patents claim the non-invasive measurement of blood glucose using modified light radiation. U.S. Pat. No. 4,704,029, issued Nov. 3, 1987 to Van Heuvelen, discloses the measurement of blood glucose by utilizing a refractometer. U.S. Pat. No. 5,448,992, issued Sep. 12, 1995 to Kupershmidt, bases measurements on a polarized-modulated laser. U.S. Pat. No. 5,433,197 to Stark describes non-invasive glucose measurement using irradiation of the eye. There are many other such references, but none relate specifically to the technique of this application.
U.S. Pat. No. 4,805,623, issued Feb. 21, 1989 to Jobsis, describes a spectrophotometric method of determining the concentration of a dilute component together with a reference component of known concentration. While not similar to the technology here disclosed, the patent teaches that obtaining an appropriate reference component is often problematic. The technique outlined in the present application obviates this lack of reference components for many cases, as determination of the concentration of many substances, such as hemoglobin level, in blood or other environments can now be done, and they in turn can serve as reference components.
U.S. Pat. No. 5,492,118, issued Feb. 20, 1996 to Gratton et al, also discloses a technique for determining material (specifically glucose) concentrations in tissues. This is done by measuring the scattering coefficient of light passed through the tissue and comparing this with a previous scattering coefficient determined with respect to the tissue.
U.S. Pat. No. 5,402,777, issued Apr. 4, 1995 to Warring et al, describes a device to facilitate non-invasive oxygen monitoring. This is a sensor system designed to improve the performance of a pulse oximeter under certain circumstances. While this may be a useful aid in standard pulse oximetry, it in no way enables any additional determinations to be made, as in the device described in the present invention.
Additionally, many patents disclose improvements to pulse oximeter probes or sensor as advances in the art. Included in this group is U.S. Pat. No. 5,469,845 DeLonzor et al, and many others.
3. Physiology and Biochemistry Background
This section refers specifically to hemoglobin and oximetry. Changes in many other substances secondary to thermal effects also occur, and measurements and determinations based on these effects are meant to be included within the scope of this patent application.
Hemoglobin is the molecule which is essentially entirely responsible for carrying oxygen in all vertebrates and some invertebrates (See; Nunn's Applied Respiratory Physiology, Cambridge, Mass.; Butterworth-Heinemann, 4th Edition (1993), Chapter 10, pp 219-246); the remainder of this discussion will be limited to humans. It is contained in the red blood cell (RBC, erythrocyte), which is the most common cell in the body. A molecule or single unit of hemoglobin (Hb) contains 4 iron groups, each of which can bind 1 molecule or unit of oxygen. Because there are 4 iron groups, a molecule of Hb can contain from 0 to 4 molecules of O.sub.2. Hb which is carrying O.sub.2 is known as oxyhemoglobin (HbO.sub.2), Hb not carrying oxygen in known as deoxyhemoglobin. The relative number of O.sub.2 molecules bound to a Hb molecule is referred to as saturation, expressed in percentage. Of course, blood is composed of billions and billions of RBCs and Hb molecules, so the averaged saturation can take on any value from 0 to 100%.
How well Hb is saturated with O.sub.2 depends mainly on the "partial pressure" of oxygen in the blood. The higher the pressure of oxygen in the blood (PO.sub.2), the higher the saturation (SO.sub.2). However, the relationship between PO.sub.2 and SO.sub.2 is not linear (change in one is not always directly proportional to change in the other). The dependence is described by a S-shaped "sigmoid" curve, common in the biologic sciences. This particular curve is call the Hemoglobin-Oxygen Dissociation Curve (HODC; see FIG. 1). Hb absorbs O.sub.2 in the lungs (to form HbO.sub.2). As the RBC travels to the tissues, the HbO.sub.2 releases oxygen.
Determination of the physiological parameters is a very important part of modern medical practice. Unfortunately, measurement of any of these parameters has until recently always required a blood sample (arterial and/or venous) to be drawn, which is then analyzed by a laboratory.
During the 1970's the first pulse oximeter was introduced. This device made use of spectrophotometry to allow approximation of arterial oxygen saturation (SaO.sub.2), termed SpO.sub.2 (saturation measured by pulse oximetry), by noninvasive means. After improvements, pulse oximeters are now commonplace in acute health care settings.
Pulse oximeter design and function are well documented. The two principal forms of Hb (oxy and deoxy: Hb and HbO.sub.2) absorb different wavelengths of light to varying degrees. The standard oximeter utilizes 2 wavelengths, one in the "red" portion of the light spectrum and the other in the near-infrared. The absorbance of emissions from light-emitting diodes (LEDs) of appropriate wavelength is measured. The pulsatile (AC) and non-pulsatile (DC) components are calculated and compared, and the ratio of the corrected signal is collated to a stored calibration curve to yield SpO.sub.2.
Transcutaneous monitoring of oxygen and carbon dioxide is also used as discussed in S. J. Barker, "Monitoring Oxygen and Carbon Dioxide", International Anesthesia Research Society, March 1996, pp 1-7, but there are several practical difficulties with this technology. It is dependent upon cardiac output and skin perfusion, the electrode must be calibrated before application to the skin, and the sensor's membrane and electrolyte must be replaced periodically. The only significant application has been found in neonatology.
There are many references disclosing noninvasive determination of glucose. However, no device has yet found acceptance in the marketplace for this function.
There have also been numerous attempts at monitoring using miniaturized probes passed through arterial cannulae. The first approach employed Clark electrodes, the same oxygen electrode used In the laboratory blood-gas analyzer. More recently, the principle of florescence quenching has been used to develop fiberoptic "optodes" which can continuously monitor pH and PCO.sub.2 as well as PO.sub.2 through an arterial cannula. Unfortunately, there have been some technical problems with optode accuracy and reliability. While this technology will no doubt improve, it remains very costly and is of course invasive in nature.
Thus, the SO.sub.2 can now be determined noninvasively. However, still the only way to determine pH and other parameters accurately has been by drawing a blood sample and utilizing laboratory analysis. Such analysis is obviously invasive (requires breaking the skin; any time the skin barrier is ruptured inflammation and/or infection can ensue), very painful (puncture of an artery is technically more difficult and much more painful than puncture of a vein, which is how most blood tests are performed), risks blood contamination for both the subject and the person drawing the blood, and creates toxic medical waste (syringe, needle, gloves, skin dressing, test tube or other container). It is expensive to perform, not only from the supplies and the cost of the analyzer making the measurement, but the operation of the analyzer and the drawing of the blood both require trained personnel. The analyzer must be calibrated frequently with chemical reagents which are costly and must be disposed of safely. Arterial puncture is also inherently dangerous, as it can cause a clot in the artery, and prevent blood flow "downstream", thus depriving those tissues of oxygen.
Therefore, it would be an advance in the art to provide a system and method to noninvasively and quantitatively assess acid-base balance and related variables. It would be another advance in the art to noninvasively and quantitatively measure hemoglobin level ("blood count") and oxygen content and capacity. It would be yet another improvement in the art to determine all these parameters rapidly and continuously. It would be of great betterment to make these measurements without the need for laboratory analysis, equipment, and personnel. It would be an progression to have a device with such capabilities that is easily transportable that could be used in an ambulance or when conveying a patient from one location to another.
It would be a further advance to have a device for immediate diagnosis of poisoning such as that due to carbon monoxide. It would be advantageous to allow rapid noninvasive screening of blood disorders such as sickle cell anemia.